crossing96/oncoscreening huggingface dataset:
Sialyl Tn-expressing bladder cancer cells induce a tolerogenic phenotype in innate and adaptive immune cells.	Despite the wide acceptance that glycans are centrally implicated in immunity, exactly how they contribute to the tilt immune response remains poorly defined. In this study, we sought to evaluate the impact of the malignant phenotype-associated glycan, sialyl-Tn (STn) in the function of the key orchestrators of the immune response, the dendritic cells (DCs). In high grade bladder cancer tissue, the STn antigen is significantly overexpressed and correlated with the increased expression of ST6GALNAC1 sialyltransferase. Bladder cancer tissue presenting elevated expression of ST6GALNAC1 showed a correlation with increased expression of CD1a, a marker for bladder immature DCs and showed concomitant low levels of Th1-inducing cytokines IL-12 and TNF-α. In vitro, human DCs co-incubated with STn(+) bladder cancer cells, had an immature phenotype (MHC-II(low), CD80(low) and CD86(low)) and were unresponsive to further maturation stimuli. When contacting with STn(+) cancer cells, DCs expressed significantly less IL-12 and TNF-α. Consistent with a tolerogenic DC profile, T cells that were primed by DCs pulsed with antigens derived from STn(+) cancer cells were not activated and showed a FoxP3(high) IFN-γ(low) phenotype. Blockade of STn antigens and of STn(+) glycoprotein, CD44 and MUC1, in STn(+) cancer cells was able to lower the induction of tolerance and DCs become more mature. Overall, our data suggest that STn-expressing cancer cells impair DC maturation and endow DCs with a tolerogenic function, limiting their capacity to trigger protective anti-tumour T cell responses. STn antigens and, in particular, STn(+) glycoproteins are potential targets for circumventing tumour-induced tolerogenic mechanisms.	bladder
Predictors of preoperative delays before radical cystectomy for bladder cancer in Quebec, Canada: a population-based study.	OBJECTIVES: To characterise and measure different components of preoperative delays experienced by patients with bladder cancer before radical cystectomy (RC) in the province of Quebec, Canada and to identify the predictors of long waiting times. METHODS: We conducted a retrospective cohort study using the data of patients who underwent RC for bladder cancer between 2000 and 2009 in Quebec. The cohort was obtained with the linkage of two provincial health databases: the Régie de l'assurance maladie du Québec database (data on medical services dispensed to Quebec residents), and the Fichier des évenements démographiques de l'Institut de la statistique du Québec database (demographic data on births and deaths). For the entire cohort, we determined several components of delay from first medical visit related to bladder cancer symptoms until RC. Predictors of long delays were analysed using logistic regression. RESULTS: We analysed a total of 2778 patients who met the inclusion criteria. The median urologist referral delay was 32 days. The median delays between first urologist visit and RC and between transurethral resection of bladder tumour (TURBT) to RC were 90 days and 46 days, respectively. The median overall delay was 116 days. All components of delay progressively increased from the decade of the 1990s to the decade of the 2000s. Male gender was a protective factor for several components of delay, which suggests that gender-related variations may exist in the course of care for bladder cancer (odds ratio 0.67, 95% CI 0.50-0.89 for overall delay). Patient age and gender were associated with delayed urologist referral, delayed time to TURBT, and long overall waiting time. Factors related to the health system were associated with long cystoscopy delays. CONCLUSION: Median preoperative delays among patients with bladder cancer have been increasing and remain unacceptably long. Patient's age, gender and type of hospital facility were associated with long waiting times.	bladder
Whorled Urothelial Cell Carcinoma: A Neglected Variant.	Twelve cases of urothelial cell papillary carcinoma with a whorled pattern of growth are described. This variant is reported with clinicopathological correlations and immunohistochemical findings. All cases showed this peculiar and distinctive curlicue histological pattern, ranging from 50% to 100% of the neoplastic population. Despite the disordered/turbulent growth pattern, the cytological grade was uniformly low. All the lesions were Ta staged and no patient experienced progression after transurethral resection, while 2 showed clinical recurrences. The immunophenotype (low p53, high p27, low Ki67, and high GATA3) of the cases contributes to define this rare variant as a low-grade tumor.	bladder
Delayed spontaneous perforation of urinary bladder with intraperitoneal seeding following radical transurethral resection of invasive urothelial cancer: a case report.	BACKGROUND: Transurethral resection of bladder tumor (TURBT) may be applicable for the treatment of deeply invasive tumors in high-risk patients who are not suitable candidates for radical cystectomy. Intraperitoneal perforation is much less common, however, bladder wall perforation is still a cause for concerns because after perforation several studies have been reported to have peritoneal or abdominal metastases. CASE PRESENTATION: An 84-year-old female patient with multiple large enhancing masses in the urinary bladder underwent radical TURBT to remove the deeply invasive tumors because she was not a suitable candidate for a major operation. Microscopic examination of the resected specimen confirmed the muscle invasive urothelial carcinoma with partial invasion into the perivesical fat tissue. She visited again 6 months later after the operation complaining abdominal distension. Computed tomography showed perforation of urinary bladder with intraperitoneal seeding and adnexa metastasis. CONCLUSION: Radical TURBT could be associated with delayed perforation of urinary bladder and intraperitoneal seeding.	bladder
Loss of MTUS1/ATIP expression is associated with adverse outcome in advanced bladder carcinomas: data from a retrospective study.	BACKGROUND: Seventy percent of all bladder tumours tend to recur and need intensive surveillance, and a subset of tumours progress to muscle-invasive and metastatic disease. However, it is still difficult to find the adequate treatment for every individual patient as it is a very heterogeneous disease and reliable biomarkers are still missing. In our study we searched for new target genes in the critical chromosomal region 8p and investigated the potential tumour suppressor gene candidate MTUS1/ATIP in bladder cancer. METHODS: MTUS1 was identified to be the most promising deleted target gene at 8p in aCGH analysis with 19 papillary bladder tumours. A correlation with bladder cancer was further validated using immunohistochemistry of 85 papillary and 236 advanced bladder tumours and in functional experiments. Kaplan-Meier analysis and multivariate Cox-regression addressed overall survival (OS) and disease-specific survival (DSS) as a function of MTUS1/ATIP expression. Bivariate correlations investigated associations between MTUS1/ATIP expression, patient characteristics and histopathology. MTUS1 expression was analysed in cell lines and overexpressed in RT112, where impact on viability, proliferation and migration was measured. RESULTS: MTUS1 protein expression was lost in almost 50% of all papillary and advanced bladder cancers. Survival, however, was only influenced in advanced carcinomas, where loss of MTUS1 was associated with adverse OS and DSS. In this cohort, there was also a significant correlation of MTUS1 expression and histological subtype: positive expression was detected in all micropapillary tumours and aberrant nuclear staining was detected in a subset of plasmocytoid urothelial carcinomas. MTUS1 was expressed in all investigated bladder cell lines and overexpression in RT112 led to significantly decreased viability. CONCLUSIONS: MTUS1 is a tumour suppressor gene in cultured bladder cancer cells and in advanced bladder tumours. It might represent one new target gene at chromosome 8p and can be used as an independent prognostic factor for advanced bladder cancer patients. The limitation of the study is the retrospective data analysis. Thus, findings should be validated with a prospective advanced bladder tumour cohort.	bladder
Clinical significance of survivin expression in patients with urothelial carcinoma.	BACKGROUND: Survivin is a member of the inhibitors of apoptosis protein family that plays an important role in carcinogenesis. Here, we examined the association between survivin expression and clinical outcome in urothelial carcinoma of the bladder (UCB). METHODS: A total of 56 histopathologically confirmed UCB patients were recruited from the Department of Urology of Chiayi Christian Hospital from August 2007 to May 2009. Immunohistochemistry (IHC) was used to detect the survivin expression in tumor tissues. The -31 C/G polymorphism in survivin promoter region was determined by polymerase chain reaction-restricted fragment length polymorphism. RESULTS: The frequency of high survivin expression was significantly higher in muscle-invasive tumors (66.6%) than in non-muscle-invasive tumors (34.2%) (P = 0.042) and in poorly differentiated (85.7%) tumors than in moderately differentiated tumors (30.8%) (P = 0.0014). The higher frequency of risk genotypes (C/C and C/G) was found in the median (72.7%) and high (68.0%) survivin expression groups. The multivariate analysis showed that a high survivin expression level was a potential predictive biomarker of poor overall survival (P = 0.02). CONCLUSION: Our results suggest that the high survivin expression was associated with tumor stage and grade and may present a predictive marker of overall survival in UCB.	bladder
Comparative effectiveness of transurethral resection of bladder tumors and office fulguration for recurrent bladder tumors.	Evaluation of: Park DS, Hwang JH, Gong IH et al. An analysis of the efficacy, safety, and cost-effectiveness of fulguration under local anesthesia for small-sized recurrent masses: a comparative analysis of transurethral resection of bladder tumors in a matched cohort. J. Endourol. 27(10), 1240-1244 (2013). At initial diagnosis, most bladder tumors are nonmuscle invasive. Some will recur after initial resection and will require transurethral resections of the bladder tumor. Fulguration under local anesthesia represents an alternative. This option is assessed in the article of Park et al. with respect to efficacy, safety and cost-effectiveness in patients with small-sized recurrent bladder tumors. The authors suggest that fulguration is safe and efficacious without compromising oncological outcomes in selected patients relative to formal transurethral resections of bladder tumor.	bladder
Robotic extramucosal excision of bladder wall leiomyoma.	INTRODUCTION: Multiple case reports and reviews have been described in the literature for bladder wall leiomyoma resection via different approaches. The minimally invasive partial cystectomy remains the most widely accepted technique; however, case reports for enucleation of bladder wall leiomyoma have also been described. The purpose of this video is to demonstrate the robotic extramucosal excision of a bladder wall leiomyoma, without cystotomy, but with complete removal of the muscular layer. MATERIALS AND METHODS: A 35-year old male present with lower urinary tract symptoms and imaging showed bladder wall mass with histopathology showed leiomyoma. The patient consented for mass excision with the possibility of a partial cystectomy. The patient was placed in the supine, 30-degree Trendelenburg position during the procedure. A total of 4 ports were inserted. A 3-arm da Vinci robotic surgical system was docked, and the arms were connected. Extramucosal excision was accomplished without cystotomy and muscle approximation was achieved by 2 0 Vicryle. RESULT: The operative time was 90 minutes, blood loss of approximately 50mL and the patient was discharged after 72 hours with no immediate complications and a 6 months follow-up showed no recurrence. CONCLUSION: Such a technique results in complete excision of the tumor, without cystotomy, and also maintains an intact mucosa. These steps, in addition to decreasing the risk of local recurrence, also shorten the period of postoperative catheterization and hospitalization.	bladder
Outcomes of radical cystectomy and bladder preservation treatment for muscle-invasive urothelial carcinoma of the bladder.	OBJECTIVE: To compare the survival outcome of various treatment modalities for organ-confined muscle-invasive urothelial carcinoma of the bladder. METHODS: One hundred and fifty patients with Stage II (T2, N0, M0) or Stage III (T3a-T4a, N0, M0) urothelial carcinoma of the bladder treated at the National Referral Hospital and the National Cancer Center of Indonesia from 1995 to 2010 with a minimum follow-up period of 24 months were included in this study. Overall survival and mean survival times were analyzed using the Kaplan-Meier method. RESULTS: The mean ± standard deviation age of the patients in this study was 57.15 ± 11.6 years and 88% were men. Over 50% of patients had T2 disease, 24.2% had T3 disease, and 21.5% had T4 disease based on pathology. Based on histological grade, 30.8% were intermediate grade tumors and 42.1% were high-grade tumors. Radical cystectomy was performed in 20 patients (13.3%) and 40 patients (26.7%) were treated with radiotherapy. Ninety (60%) patients underwent transurethral resection of the bladder tumor only without further definitive treatment for personal reasons. The actuarial 5-year overall survival for all patients was as follows: radical cystectomy, 50%; radiotherapy, 22.7%; and transurethral resection of the bladder tumor only, 8.3% (log-rank p = 0.029). For stage T2 patients, the 5-year overall survival was: radical cystectomy, 62.5%; radiotherapy, 31.2%; and transurethral resection of the bladder tumor only, 8.3% (log-rank p = 0.017). CONCLUSION: In our series, radical cystectomy had a superior outcome to radiotherapy or transurethral resection of the bladder tumor only, comparable with results reported elsewhere. Radical cystectomy should be offered as the gold standard treatment for organ-confined muscle-invasive urothelial carcinoma of the bladder.	bladder
Intermediate-term oncologic outcomes of robot-assisted radical cystectomy for urothelial carcinoma.	PURPOSE: To evaluate intermediate-term oncologic outcomes in a large series of patients who were treated with robot-assisted radical cystectomy (RARC) for urothelial carcinoma of the bladder (UCB). PATIENTS AND METHODS: Between 2004 and 2010, 162 patients underwent RARC at City of Hope Cancer Center for UCB and were analyzed with respect to overall (OS), disease-specific (DSS), and disease-free survival (DFS). Descriptive statistics were used to summarize demographics and perioperative variables. The Kaplan-Meier method was used to estimate survival and recurrence. Univariable and multivariable Cox proportional hazards regression models were used to determine predictors of survival. RESULTS: Median follow-up was 52 months. Thirty-eight (23.4%) patients received neoadjuvant chemotherapy before RARC; 28% of patients were pT2 and 33% had final pathology status of pT3 or pT4. Median lymph node count was 28, and positive surgical margin rate was 4.3%. Local recurrence occurred in 11 (6.8%) patients. OS, DFS, and DSS at 3 years were 61%, 76%, and 83%, respectively. OS, DFS, and DSS at 5 years were 54%, 74%, and 80%, respectively. Predictors of OS and DFS on multivariable analysis were lymph node density, pathologic stage, and age-adjusted Charlson Comorbidity Index, while receipt of transfusion was also a negative predictor of OS. CONCLUSIONS: RARC provides an effective means of treatment of UCB in a minimally invasive fashion with comparable oncologic outcomes to that reported in the literature of open procedures.	bladder
S1PR1 is crucial for accumulation of regulatory T cells in tumors via STAT3.	S1PR1 signaling has been shown to restrain the number and function of regulatory T (Treg) cells in the periphery under physiological conditions and in colitis models, but its role in regulating tumor-associated T cells is unknown. Here, we show that S1PR1 signaling in T cells drives Treg accumulation in tumors, limits CD8(+) T cell recruitment and activation, and promotes tumor growth. T-cell-intrinsic S1PR1 affects Treg cells, but not CD8(+) T cells, as demonstrated by adoptive transfer models and transient pharmacological S1PR1 modulation. An increase in S1PR1 in CD4(+) T cells promotes STAT3 activation and JAK/STAT3-dependent Treg tumor migration, whereas STAT3 ablation in T cells diminishes tumor-associated Treg accumulation and tumor growth. Our study demonstrates a stark contrast between the consequences of S1PR1 signaling in Treg cells in the periphery versus tumors.	bladder
Dermatological exposure to coal tar and bladder cancer risk: a case-control study.	OBJECTIVE: Coal tar ointments are used as treatment of various skin diseases, especially psoriasis and eczema. These ointments contain several carcinogenic polycyclic aromatic hydrocarbons. Metabolites of these polycyclic aromatic hydrocarbons are excreted in the urine and therefore, dermatological use of coal tar may be associated with an increased risk of bladder cancer. The objective of this study was to evaluate the association between dermatological use of coal tar ointments and bladder cancer. MATERIAL AND METHODS: A population-based case-control study was conducted including 1,387 cases diagnosed with bladder cancer and 5,182 population controls. Information on the use of coal tar, history of skin disease, and known risk factors for bladder cancer was obtained through postal questionnaires. Logistic regression analyses were performed to estimate the risk of bladder cancer after coal tar treatment, adjusted for age, gender, smoking status, duration of smoking, and intensity of smoking. RESULTS: The use of coal tar ointments was approximately equal among cases and controls (3.8% vs. 3.0%, respectively). Dermatological application of coal tar was not significantly associated with bladder cancer (adjusted odds ratio = 1.37, 95% CI: 0.93-2.01). An inverse association between bladder cancer and a history of skin disease was observed (adjusted odds ratio = 0.74, 95% CI: 0.61-0.90). CONCLUSION: This is the first study with a specific aim to study the association between the use of coal tar preparations and bladder cancer. The results suggest that there is no reason for safety concerns with respect to the risk of bladder cancer after the use of coal tar preparations in dermatological practice.	bladder
Phosphorylated p70S6K in noninvasive low-grade urothelial carcinoma of the bladder: correlation with tumor recurrence.	We investigated whether inhibiting phosphorylated p70S6K (p-p70S6K) suppresses the proliferation and growth of noninvasive low-grade urothelial carcinoma (LG-URCa) in vitroand whether p-p70S6K can serve as a predictive biomarker for the recurrence of noninvasive LG-URCa of the bladder in patients. We constructed a tissue microarray (TMA) for 95 LG-URCa and 35 benign urothelium samples and performed immunohistochemical staining for p-p70S6K and p-4E-BP1. A Cox regression model was used to investigate the predictive factors for recurrence of LG-URCa. We investigated the dose-dependent antiproliferative effect of rapamycin, its antiproliferative effect and the growth-inhibition effect of p70S6K siRNA transfection in RT4 and 253J cell lines. The pT1 staged group (P < 0.05; hazard ratio (HR), 2.415) and the high p-p70S6K staining group (P < 0.05; HR, 2.249) were independent factors for predicting recurrence. Rapamycin inhibited RT4 and 253J cell proliferation in a dose-dependent manner (r = -0.850, P< 0.001 in RT4 cells; r = -0.835, P< 0.001 in 253J cells). RT4 and 253J cell proliferation and growth were inhibited by the transfection of p70S6K siRNA and rapamycin, respectively (P < 0.05). Transfection of p70S6K siRNA resulted in inhibitory effects on cell proliferation and growth that were similar to those of rapamycin. Our results suggest that inhibiting p70S6K phosphorylation is important to prevent recurrence and that p70S6K phosphorylation can be used as a molecular biomarker to predict recurrence of certain LG-URCa of the bladder.	bladder
Next-generation sequencing identifies germline MRE11A variants as markers of radiotherapy outcomes in muscle-invasive bladder cancer.	BACKGROUND: Muscle-invasive bladder cancer (MIBC) can be cured by radical radiotherapy (RT). We previously found tumour MRE11 expression to be predictive of survival following RT in MIBC, and this was independently validated in a separate institute. Here, we investigated germline MRE11A variants as possible predictors of RT outcomes in MIBC, using next-generation sequencing (NGS). PATIENTS AND METHODS: The MRE11A gene was amplified in germline DNA from 186 prospectively recruited MIBC patients treated with RT and sequenced using bar-coded multiplexed NGS. Germline variants were analysed for associations with cancer-specific survival (CSS). For validation as a prognostic or predictive marker, rs1805363 was then genotyped in a cystectomy-treated MIBC cohort of 256 individuals. MRE11A mRNA isoform expression was measured in bladder cancer cell lines and primary tumour samples. RESULTS: Carriage of at least one of six (five novel) rare variants was associated with the worse RT outcome (hazard ratio [HR] 4.04, 95% confidence interval [95% CI] 1.42-11.51, P = 0.009). The single-nucleotide polymorphism (SNP), rs1805363 (minor allele frequency 11%), was also associated with worse CSS (per-allele HR 2.10, 95% CI 1.34-3.28, Ptrend = 0.001) following RT in MIBC, with a gene-dosage effect observed, but no effect seen on CSS in the cystectomy cohort (Ptrend = 0.89). Furthermore, rs1805363 influenced relative MRE11A isoform expression, with increased isoform 2 expression with carriage of the rs1805363 minor A allele. CONCLUSIONS: Germline MRE11A SNP rs1805363 was predictive of RT, but not of cystectomy outcome in MIBC. If successfully validated in an independent RT-treated cohort, this SNP could be a useful clinical tool for selecting patients for bladder-conserving treatment.	bladder
Optimizing intravesical mitomycin C therapy in non-muscle-invasive bladder cancer.	Nearly three-quarters of all newly diagnosed urothelial cancers are non-muscle-invasive bladder cancers (NMIBCs). Although bladder-preserving surgery can be used to treat NMIBC, the rate of recurrence remains high. Intravesical chemotherapy has been shown to reduce the rate of NMIBC recurrence, and mitomycin C (MMC) has become the most commonly used intravesical cytotoxic agent. Despite the popularity of this agent in the treatment of NMIBCs, many questions regarding the optimal approach to MMC therapy remain unanswered. Strategies to enhance delivery of MMC have been well studied and multiple measures are recommended for implementation in routine clinical practice. In addition, less widely investigated techniques, such as hyperthermia and electromotive drug administration, have been shown to increase the efficacy of MMC therapy. Nevertheless, even when the current 'optimal' approaches to MMC administration are used, a large proportion of NMIBCs recur. This apparent treatment resistance might be overcome by combination of MMC with other agents that have different mechanisms of action and are unlikely to have cross-resistance. Study of the mechanisms of resistance is, therefore, important to identify key pathways underlying this phenomenon, which could be rationally targeted using specific combinations of drugs. Knowledge of these mechanisms might also reveal markers of responsiveness to therapy that could be used for patient selection.	bladder